scholarly journals The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile

2021 ◽  
Vol 7 (28) ◽  
pp. eabf4408
Author(s):  
Jean Berthelet ◽  
Verena C. Wimmer ◽  
Holly J. Whitfield ◽  
Antonin Serrano ◽  
Thomas Boudier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Cancer Progression ◽  
Molecular Heterogeneity ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Interactive Network ◽  
Factor Α ◽  
Clonal Composition

Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor–α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.

scholarly journals In vivo single scan detection of both iron-labeled cells and breast cancer metastases in the mouse brain using balanced steady-state free precession imaging at 1.5 T

2011 ◽  
Vol 34 (1) ◽  
pp. 231-238 ◽  
Author(s):  
Emeline J. Ribot ◽  
Francisco M. Martinez-Santiesteban ◽  
Carmen Simedrea ◽  
Patricia S. Steeg ◽  
Ann F. Chambers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Mouse Brain ◽  
Steady State Free Precession ◽  
Free Precession ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Free Precession Imaging ◽  
Scan Detection

scholarly journals Stereotactic radiotherapy of breast cancer liver metastases

2021 ◽  
Vol 67 (3) ◽  
pp. 382-390
Author(s):  
Sergei Tkachev ◽  
Sevil Alieva ◽  
Sergey Medvedev ◽  
Aleksei Nazarenko ◽  
Denis Romanov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Stereotactic Radiotherapy ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Breast Cancer Liver Metastases

Stereotactic body radiation therapy currently occupies its place in the complex treatment of cancer patients with liver metastases. It is assumed that certain groups of patients with breast cancer can benefit from the use of this method, which can be converted into improved overall survival and survival rates without signs of progression of the process. Purpose of the study was to evaluate the efficacy and tolerability of stereotactic radiotherapy in patients with breast cancer metastases in the liver. We have analyzed the results of using stereotactic radiotherapy in 25 breast cancer patients with 43 liver metastases. The treatment was carried out in 3 fractions with a fraction dose of 10-15 Gy and a total dose of 30-45 Gy. Growth of the irradiated lesions was recorded only in 1 case out of 43 metastases (2,3%) and 25 (4%) patients. 1-, 3- and 5-year overall survival rates from the moment of stereotactic radiotherapy were 82,9%, 62% and 38,7%, respectively. Long-term post-radiation adverse events were observed in 8% of cases and did not have a significant effect on the quality of life and the possibility of antitumor treatment. So stereotactic radiotherapy can be recommended as a relatively safe and highly effective method of elimination of breast cancer liver metastases. Taking into account the high achieved local control, further studies on dose escalation in this group of patients are not required.  

scholarly journals PKM2 Promotes Breast Cancer Progression by Regulating Epithelial Mesenchymal Transition

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hui Xiao ◽  
Longxiao Zhang ◽  
Yuan Chen ◽  
Chengjun Zhou ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Mesenchymal Transition ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Glucose Intake ◽  
Cancer Tissues

Breast cancer is the leading cause of females characterized by high invasive potential. It is necessary to explore the underlying mechanism of breast cancer metastases and to find specific therapeutic targets. PKM2 is considered a new biomarker of cancer with upregulated expression in tumor tissue. PKM2 participates in the cancer-specific Warburg effect to regulate fast glucose intake consumption. Besides, PKM2 also contributes to cancer progression, especially tumor metastasis. In this study, we showed that PKM2 is upregulated in breast cancer tissues and the upregulating of PKM2 in breast cancer correlates with poor prognosis. PKM2 can regulate tumor progression by promoting tumor cell viability and mobility. Furthermore, overexpression of PKM2 can promote EMT to encourage tumor metastasis. These findings indicate PKM2 is a potentially useful diagnostic biomarker and therapeutic target in breast cancer.

scholarly journals BET inhibition increases βIII-tubulin expression and sensitizes metastatic breast cancer in the brain to vinorelbine

2020 ◽  
Vol 12 (558) ◽  
pp. eaax2879
Author(s):  
Deepak Kanojia ◽  
Wojciech K. Panek ◽  
Alex Cordero ◽  
Jawad Fares ◽  
Annie Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
In Silico Analysis ◽  
In Vivo Studies ◽  
Neoplastic Cells ◽  
Systematic Analysis ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
The Brain

Metastases from primary breast cancer result in poor survival. βIII-tubulin (TUBB3) has been established as a therapeutic target for breast cancer metastases specifically to the brain. In this study, we conducted a systematic analysis to determine the regulation of TUBB3 expression in breast cancer metastases to the brain and strategically target these metastases using vinorelbine (VRB), a drug approved by the U.S. Food and Drug Administration (FDA). We found that human epidermal growth factor receptor 2 (HER2) signaling regulates TUBB3 expression in both trastuzumab-sensitive and trastuzumab-resistant neoplastic cells. We further discovered that bromodomain and extra-terminal domain (BET) inhibition increases TUBB3 expression, rendering neoplastic cells more susceptible to apoptosis by VRB. Orthotopic xenograft assays using two different breast cancer cell models revealed a reduction in tumor volume with BET inhibition and VRB treatment. In addition, in vivo studies using a model of multiple brain metastasis (BM) showed improved survival with the combination of radiation + BET inhibitor (iBET-762) + VRB (75% long-term survivors, P < 0.05). Using in silico analysis and BET inhibition, we found that the transcription factor myeloid zinc finger-1 (MZF-1) protein binds to the TUBB3 promoter. BET inhibition decreases MZF-1 expression and subsequently increases TUBB3 expression. Overexpression of MZF-1 decreases TUBB3 expression and reduces BM in vivo, whereas its knockdown increases TUBB3 expression in breast cancer cells. In summary, this study demonstrates a regulatory mechanism of TUBB3 and provides support for an application of BET inhibition to sensitize breast cancer metastases to VRB-mediated therapy.

Liver Surgery for Breast Cancer Metastases

2009 ◽  
Vol 69 (05) ◽  
Author(s):  
EC Schest ◽  
H Cerwenka ◽  
A El-Shabrawi ◽  
H Bacher ◽  
HJ Mischinger
Keyword(s):  
Breast Cancer ◽  
Liver Surgery ◽  
Breast Cancer Metastases ◽  
Cancer Metastases

Deprivation of the vitamin D receptor (VDR) fuels breast cancer metastases to bone

2019 ◽  
Author(s):  
K Horas ◽  
M Abraham ◽  
F Jakob ◽  
R Ebert ◽  
G Maier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Breast Cancer Metastases ◽  
Cancer Metastases

Olfactomedin-like 2A, 2B and 3 are differentially expressed in breast cancer metastases.

2019 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Genetically Engineered ◽  
Differentially Expressed ◽  
Genetically Engineered Mouse Models ◽  
Breast Cancer Metastases ◽  
Multiple Datasets ◽  
Cancer Metastases ◽  
Distant Organ ◽  
Metastatic Process ◽  
Differential Gene

Differential gene expression analysis of multiple datasets, in mice and in men revealed that transcripts of the olfactomedin-like family are differentially expressed in metastases, both in patients with breast cancer and in genetically engineered mouse models of breast cancer. The expression of olfactomedin-like genes was perturbed in metastases to the bone, brain and the lung, suggesting that these molecules function in the metastatic process rather than having tissue-specific associations with the site of dissemination. The olfactomedin-like family may play a role in the progression of breast cancer from frank tumor to colonization of distant organ sites.

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